iNOS inhibitor and nab-paclitaxel in combination with alpelisib. for Metastatic Breast Cancer

Phase-Based Progress Estimates
1
Effectiveness
2
Safety
Metastatic Breast Cancer+3 MoreL-NMMA - Drug
Eligibility
18+
All Sexes
What conditions do you have?
Select

Study Summary

This is a research study to test the safety and effectiveness of using the drug alpelisib together with chemotherapy (nab-paclitaxel) and a drug called L-NMMA in patients with HER2 negative metastatic or locally advanced metaplastic breast cancer, who have not responded to previous treatments. Participants in this study in addition to the standard care chemotherapy will also receive the drug alpelisib and L-NMMA. The therapies will be administered every 3 weeks (1 cycle) until disease progression, toxicity or until the participant withdraws from the study. The nab-paclitaxel chemotherapy will be administered intravenously on Day 1 of the 3 week cycles. Participants will take the drug alpelisib by mouth once daily at a dose determined by a safety study and the drug L-NMMA will be given intravenously on days 1 to 5 of the 3 week cycles.

Eligible Conditions
  • Breast Cancer
  • Metastatic Breast Cancer
  • Metaplastic Breast Cancer
  • HER2-negative Breast Cancer

Treatment Effectiveness

Study Objectives

2 Primary · 4 Secondary · Reporting Duration: The RP2D will be defined as the highest dose administered at which 6 patients complete treatment with experiencing <2 DLTs (Study completion is an average of 6 cycles, determined by diseases progression, unacceptable toxicity, physician's discretion)

Day 21
PIK3CA mutation
Study treatment will continue until progression, unacceptable toxicity, treating physician's discretion, or patient withdraws from the study. An average of 6 cycles q3week.
Analysis of responses to an iNOS inhibitor and nab-paclitaxel in combination with alpelisib.
OS of patients with HER2 negative metastatic or locally advanced MpBC
Objective response rate (ORR)
PFS of patients with HER2 negative metastatic or locally advanced MpBC
The RP2D will be defined as the highest dose administered at which 6 patients complete treatment with experiencing <2 DLTs (Study completion is an average of 6 cycles, determined by diseases progression, unacceptable toxicity, physician's discretion)
Define recommended phase II dose (RP2D)

Trial Safety

Safety Progress

2 of 3
This is further along than 68% of similar trials

Side Effects for

Sitagliptin Plus Pegvisomant
20%Dizziness and paresthesias during arginine infusion
20%Abdominal cramping and diarrhea
This histogram enumerates side effects from a completed 2017 Phase 4 trial (NCT01701973) in the Sitagliptin Plus Pegvisomant ARM group. Side effects include: Dizziness and paresthesias during arginine infusion with 20%, Abdominal cramping and diarrhea with 20%.

Trial Design

1 Treatment Group

iNOS inhibitor and nab-paclitaxel in combination with alpelisib.
1 of 1

Experimental Treatment

36 Total Participants · 1 Treatment Group

Primary Treatment: iNOS inhibitor and nab-paclitaxel in combination with alpelisib. · No Placebo Group · Phase 2

iNOS inhibitor and nab-paclitaxel in combination with alpelisib.
Drug
Experimental Group · 1 Intervention: L-NMMA · Intervention Types: Drug
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
L-NMMA
2010
Completed Phase 4
~430

Trial Logistics

Trial Timeline

Screening: ~3 weeks
Treatment: Varies
Reporting: the rp2d will be defined as the highest dose administered at which 6 patients complete treatment with experiencing <2 dlts (study completion is an average of 6 cycles, determined by diseases progression, unacceptable toxicity, physician's discretion)

Who is running the clinical trial?

The Methodist Hospital Research InstituteLead Sponsor
239 Previous Clinical Trials
35,552 Total Patients Enrolled
1 Trials studying Metastatic Breast Cancer
24 Patients Enrolled for Metastatic Breast Cancer
Novartis PharmaceuticalsIndustry Sponsor
2,718 Previous Clinical Trials
3,525,351 Total Patients Enrolled
27 Trials studying Metastatic Breast Cancer
11,955 Patients Enrolled for Metastatic Breast Cancer
Polly A Niravath, MDPrincipal InvestigatorHouston Methodist Cancer Center

Eligibility Criteria

Age 18+ · All Participants · 10 Total Inclusion Criteria

Mark “Yes” if the following statements are true for you:
Written permission is obtained from the patient (or appropriate representative) to participate in the study.
You are 18 or older on the day of consenting.
You have HER2 negative MpBC and/or Triple Negative Breast Cancer (TNBC) of squamous or sarcomatoid origin, including osseous, chondroid, and spindle morphology.
Your HER2 status meets the American Society of Clinical Oncology and College of American Pathologists standards at enrollment.
This trial is open to patients with locally advanced inoperable or metastatic MpBC who have measurable disease as per RECIST 1.1, regardless of prior immunotherapy treatment received according to standard care guidelines.
You have an Eastern Cooperative Oncology Group performance status of either 0 or 1.
Your hemoglobin level is at least 9.0 g/dl, and you have not had a blood transfusion within the past two weeks.
Your absolute neutrophil count is 1000/μL or higher without granulocyte colony stimulating factor support within 2 weeks of the laboratory test used for eligibility determination.
The platelet count is at least 100,000/μL without a transfusion within two weeks of the laboratory test used to evaluate eligibility.
Your serum total bilirubin is at or below 1.5 times the upper limit of normal, unless you have Gilbert's syndrome in which case a higher amount is acceptable.
References